Protein surface roughness and small molecular binding sites

被引：70

作者：

Pettit, FK

Bowie, JU ^{[1
]}

机构：

[1] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, UCLA DOE Lab Struct Biol & Mol Med, Los Angeles, CA 90095 USA

来源：

JOURNAL OF MOLECULAR BIOLOGY | 1999年 / 285卷 / 04期

基金：

美国国家科学基金会;

关键词：

functional sites; fractal dimension; drug design; site prediction;

D O I：

10.1006/jmbi.1998.2411

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Pharmaceutical design is usually directed at developing small molecules that can specifically bind and alter the activity of a target protein. Here, we show that high-affinity binding of small molecules requires a rough patch on a protein surface. Drug design strategies should therefore be targeted to rough areas on a protein. Our results indicate that the roughness of small functional sites may reflect the complex local shapes needed to fit specific interactions into small areas. (C) 1999 Academic Press.

引用

页码：1377 / 1382

页数：6